@article{32b807cc67054d30b787340e6eba428d,
title = "Prolonged epigenomic and synaptic plasticity alterations following single exposure to a psychedelic in mice",
abstract = "Clinical evidence suggests that rapid and sustained antidepressant action can be attained with a single exposure to psychedelics. However, the biological substrates and key mediators of psychedelics{\textquoteright} enduring action remain unknown. Here, we show that a single administration of the psychedelic DOI produces fast-acting effects on frontal cortex dendritic spine structure and acceleration of fear extinction via the 5-HT2A receptor. Additionally, a single dose of DOI leads to changes in chromatin organization, particularly at enhancer regions of genes involved in synaptic assembly that stretch for days after the psychedelic exposure. These DOI-induced alterations in the neuronal epigenome overlap with genetic loci associated with schizophrenia, depression, and attention deficit hyperactivity disorder. Together, these data support that epigenomic-driven changes in synaptic plasticity sustain psychedelics{\textquoteright} long-lasting antidepressant action but also warn about potential substrate overlap with genetic risks for certain psychiatric conditions.",
keywords = "5-HT2A receptor, GPCR, depression, epigenomics, hallucinogens, psychedelics, psychosis, schizophrenia, serotonin (5-HT), synaptic plasticity",
author = "{de la Fuente Revenga}, Mario and Bohan Zhu and Guevara, {Christopher A.} and Naler, {Lynette B.} and Saunders, {Justin M.} and Zirui Zhou and Rudy Toneatti and Salvador Sierra and Wolstenholme, {Jennifer T.} and Beardsley, {Patrick M.} and Huntley, {George W.} and Chang Lu and Javier Gonz{\'a}lez-Maeso",
note = "Funding Information: We thank Jennifer Jimenez and Yashu Sampathkumar for technical assistance with behavior assays. M.d.l.F.R. would like to dedicate this manuscript to the memory of Jordi Riba on the anniversary of his passing away. This work was supported in part by the National Institutes of Health grants R01MH084894 , R01MH111940 , and P30DA033934 (J.G.-M.), R01GM143940 (C.L.), R01NS107512 (G.W.H.), N01DA-17-8932 , and N01DA-19-8949 (P.M.B.), P50AA022537 (J.T.W.), F30MH116550 (J.M.S), T32MH087004 (C.A.G.), and T32MH020030 (M.d.l.F.R.). Funding Information: We thank Jennifer Jimenez and Yashu Sampathkumar for technical assistance with behavior assays. M.d.l.F.R. would like to dedicate this manuscript to the memory of Jordi Riba on the anniversary of his passing away. This work was supported in part by the National Institutes of Health grants R01MH084894, R01MH111940, and P30DA033934 (J.G.-M.), R01GM143940 (C.L.), R01NS107512 (G.W.H.), N01DA-17-8932, and N01DA-19-8949 (P.M.B.), P50AA022537 (J.T.W.), F30MH116550 (J.M.S), T32MH087004 (C.A.G.), and T32MH020030 (M.d.l.F.R.). M.d.l.F.R. B.Z. C.L. and J.G.-M. designed experiments, analyzed data, and wrote the manuscript. C.L. and J.G.-M. supervised the research and obtained funding. M.d.l.F.R. J.M.S. R.T. and S.S. supervised by J.G.-M. performed behavioral and synaptic structure assays. B.Z. L.B.N. and Z.Z. supervised by C.L. performed ChIP-seq and RNA-seq assays and conducted bioinformatic analysis. C.A.G. supervised by G.W.H. performed electrophysiological studies. J.T.W. and P.M.B. provided advice on behavioral assays and editorial suggestions on early drafts of the report. All authors discussed the results and commented on the manuscript prior to submission for publication consideration. J.G.-M. has a sponsored research contract with NeuRistic, and M.d.l.F.R. has a consulting agreement with Noetic. The remaining authors declare that they have no conflict of interest. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = oct,
day = "19",
doi = "10.1016/j.celrep.2021.109836",
language = "English",
volume = "37",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "3",
}